Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings

Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effecti...

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Bibliographic Details
Published in:Biomaterials 2019-03, Vol.196, p.90-99
Main Authors: Alhamdi, Jumana R., Peng, Tao, Al-Naggar, Iman M., Hawley, Kelly L., Spiller, Kara L., Kuhn, Liisa T.
Format: Article
Language:English
Subjects:
Aging
Animals
Bone repair
Calcium phosphate
Calcium Phosphates - pharmacology
Cellular Senescence - drug effects
Coated Materials, Biocompatible - pharmacology
Dose-Response Relationship, Drug
Drug delivery
Drug Delivery Systems
Gene Expression Regulation - drug effects
Humans
Interferon-gamma - pharmacology
Kinetics
Macrophages
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
Male
Mice, Inbred C57BL
Simvastatin
Simvastatin - pharmacology
THP-1 Cells
Time Factors
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Summary:Older adults suffer from weakened and delayed bone healing due to age-related alterations in bone cells and in the immune system. Given the interaction between the immune system and skeletal cells, therapies that address deficiencies in both the skeletal and the immune system are required to effectively treat bone injuries of older patients. The sequence of macrophage activation observed in healthy tissue repair involves a transition from a pro-inflammatory state followed by a pro-reparative state. In older patients, inflammation is slower to resolve and impedes healing. The goal of this study was to design a novel drug delivery system for temporal guidance of the polarization of macrophages using bone grafting materials. A biomimetic calcium phosphate coating (bCaP) physically and temporally separated the pro-inflammatory stimulus interferon-gamma (IFNγ) from the pro-reparative stimulus simvastatin (SIMV). Effective doses were identified using a human monocyte line (THP-1) and testing culminated with bone marrow macrophages obtained from old mice. Sequential M1-to-M2 activation was achieved with both cell types. These results suggest that this novel immunomodulatory drug delivery system holds potential for controlling macrophage activation in bones of older patients.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2018.07.012